Structural Biochemistry, Bijvoet Center for Biomolecular Research, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
Department of Bionanoscience, Kavli Institute of Nanoscience, Faculty of Applied Sciences, Delft University of Technology, Van der Maasweg 9, 2629 HZ, Delft, The Netherlands.
Nat Commun. 2022 Nov 3;13(1):6607. doi: 10.1038/s41467-022-34302-9.
Cell-surface expressed contactin 1 and neurofascin 155 control wiring of the nervous system and interact across cells to form and maintain paranodal myelin-axon junctions. The molecular mechanism of contactin 1 - neurofascin 155 adhesion complex formation is unresolved. Crystallographic structures of complexed and individual contactin 1 and neurofascin 155 binding regions presented here, provide a rich picture of how competing and complementary interfaces, post-translational glycosylation, splice differences and structural plasticity enable formation of diverse adhesion sites. Structural, biophysical, and cell-clustering analysis reveal how conserved Ig1-2 interfaces form competing heterophilic contactin 1 - neurofascin 155 and homophilic neurofascin 155 complexes whereas contactin 1 forms low-affinity clusters through interfaces on Ig3-6. The structures explain how the heterophilic Ig1-Ig4 horseshoe's in the contactin 1 - neurofascin 155 complex define the 7.4 nm paranodal spacing and how the remaining six domains enable bridging of distinct intercellular distances.
细胞表面表达的神经联络蛋白 1 和神经束蛋白 155 控制着神经系统的布线，并通过细胞间相互作用形成和维持连接神经纤维髓鞘的轴突结。神经联络蛋白 1-神经束蛋白 155 黏附复合物形成的分子机制尚不清楚。本文呈现了复合物和单个神经联络蛋白 1 和神经束蛋白 155 结合区域的晶体结构，为我们提供了丰富的信息，使我们了解到竞争和互补的界面、翻译后糖基化、剪接差异和结构可塑性如何使多样化的黏附位点得以形成。结构、生物物理和细胞聚类分析揭示了保守的 Ig1-2 界面如何形成竞争的异源黏附性神经联络蛋白 1-神经束蛋白 155 和同源神经束蛋白 155 复合物，而神经联络蛋白 1 则通过 Ig3-6 上的界面形成低亲和力聚集体。这些结构解释了异源黏附性 Ig1-Ig4 马蹄铁如何在神经联络蛋白 1-神经束蛋白 155 复合物中定义 7.4nm 的连接神经纤维髓鞘的轴突结间距，以及其余六个结构域如何实现不同细胞间距离的桥接。
Zotero 插件
